Human chorionic gonadotropin (HCG) (not to be confused with human growth hormone, or HGH) is a glycoprotein hormone that mimics LH (luteinizing hormone), produced in pregnancy by the developing embryo soon after conception, and later by part of the placenta. Its role is to prevent the disintegration of the corpus luteum of the ovary and to maintain the progesterone production critical for pregnancy in women. It supports the normal development of an egg in a woman's ovary, and stimulates the release of the egg during ovulation. HCG is used to cause ovulation and to treat infertility in women.
You're probably asking yourself why you should care about this. But in men, HCG is also used in young boys when their testicles have not dropped down into the scrotum normally. Additionally, HCG is used to increase testicular size after long-term testosterone or anabolic steroid use.
Testosterone replacement therapy triggers the hypothalamus to shut down its production of GnRH (gonadotropin releasing hormone). Without GnRH, the pituitary gland stops releasing LH. Without LH the testes (testicles or gonads) shut down their production of testosterone. For males HCG closely resembles LH. If the testicles have shrunken after long-term testosterone use, they will likely begin to enlarge and start their testosterone production shortly after HCG therapy is instituted. HCG jump-starts your testes to produce testosterone and to increase their size.
HCG has also been shown to increase the amount of testosterone inside the testicles (Intratesticular testosterone or IT). The use of HCG alone to increase testosterone is not as popular as using testosterone replacement due to several factors: 1- cost since large doses of HCG would be required, 2- quality of life of HCG alone vs TRT may be worse (this has not been validated by comparison studies), 3- concerns about long term high dose HCG use and its potential effect on desensitization of Leydig cells to it.
When used in small doses 2-3 times per week along with testosterone replacement, HCG can reverse the decrease of intratesticular testosterone. HCG's effect as a LH mimicker plus its ability to increase IT seem to be the reasons why men were able to preserve fertility (normal sperm) when using testosterone replacement plus 500 IU HCG every other day in Dr Lipshultz' study (see study attached to this post). The main surprising result of that study is that normal sperm quality can be preserved by this combo even in the absence of FSH, a gonadotropin thought to be essential in sperm production.
How is HCG made?
HCG can be extracted from pregnant women's urine or through genetic modification. The product is available by prescription under the brand names Pregnyl, Follutein, Profasi, and Novarel. Novire is another brand but it is a product of recombinant DNA. Compounding pharmacies can also make HCG by prescription in different vial sizes. Brand names of HCG in regular pharmacies cost over $100 per 10,000 IUs. The same amount of IUs cost around $50 in compounding pharmacies. Many insurance policies do not pay for HCG since they consider its use for testicular atrophy while on TRT an off label use. So, most men using it pay for it themselves and get it from compounding pharmacies that sell it a lot cheaper.
How is HCG supplied?
HCG is dispensed as a powder contained in vials of 3,500 IUs, 5, 000 IUs or 10,000 IUs or more (most common is actually 11,000 IU) . You can call compounding pharmacies and have them make vials for you with different IU amounts, though. These are usually accompanied by another vial of 1 mL (or cc) of bacteriostatic water to reconstitute the powder into a liquid solution.
What is an IU? When measuring testosterone we spoke in weights of grams and milligrams. HCG is measured not by weight but in IUs, or international units. IU is not about weight but refers to the amount of a substance that produces a particular biologic effect that has been agreed upon as in international standard. The IU from one substance to the next does not mean they have equivalent weights (for example, 1, 000 IU of vitamin C might have a different weight than 1,000 IU of vitamin A). Again, IU is not a weight measuring unit.
Bacteriostatic water (water with a preservative that is provided with the prescription) is mixed in with the powder to reconstitute or dissolve, it before injection. This type of water can preserve the solution for up to 6 weeks when refrigerated. Some patients do not use the 1 mL water vials that come with the commercially (non compounded) available product and instead get their doctors to prescribe 30 cc bottles of bacteriostatic water so that they can dilute the HCG down to a more workable concentration that is more practical for men using lower doses of HCG weekly.
How is HCG administered?
HCG is given as an injection under the skin or intramuscularly (there is still debate on which method is best). The number of IUs per injection will depend on how much bacteriostatic water you add to the dry powder vial. If you add 1 mL to a 5,000 IU powder vial, then you will have 5,000 IUs per mL, so 0.1 mL would be 500 IU. If you add 2 mL to the 5,000 IU dry powder vial, then you will have 2,500 IU/mL; 0.1 ml (or cc) in an insulin syringe will equal 250 IU.
Ultra-fine needle insulin syringes are used to inject HCG under the skin, making this very easy to take even for the needle-phobic. Typical sizes are:
1 ml, 12.7 mm long, 30 gauge and
0.5 ml, 8 mm, 31 gauge syringes.
Syringes require a separate prescription. Some compounding pharmacies will automatically include them with the shipment, but do not forget to ask them. Never use the syringe that you used for injecting the bacteriostatic water into the powder for injecting yourself; the needle will be dull (I usually use a regular 23 gauge, 1 inch, 3 ml syringe to load up the water). Remember that you also need alcohol pads to clean the injection area and the tip of the vial. Typical injection sites are the abdominal area close to the navel or in the pubic fat pad. Pinch a little fat on your abdominals and inject into that pinched area, then massage with an alcohol pad. Discard syringes into the sharps container that can be provided by your pharmacy.
As I mentioned before, compounded HCG is a lot cheaper than the commercially available pharmaceutical products. Sometimes it is difficult to find commercially available HCG in regular pharmacies.
Mixing Reconstitution Instructions:
HCG comes in a small bottle with a white powder. You need bacteriostatic water (provided by the compounding pharmacy) to mix it with the powder. The most common HCG vials now come with 11,000 IUs. If you have one of these, follow these instructions.
Use a large syringe provided with the product to inject 11 ml of bacteriostatic water to the vial containing the HCG dry powder, aiming against the glass vial wall. Swirl the vial with a gentle rotary motion until contents are dissolved- DO NOT SHAKE.
Suggested syringe size for injection under the skin: 30 Gauge needle of 5/16 inches in length containing 1 milliliter (30G 5/16x1ML). Note: ml = cc
How much HCG to draw depends on the dose to be used (follow physicians recommendations):
For example, for 1,000iu per dose = draw 1ml= 100 on the syringe
500iu per dose = draw 0.5ml= 50 on the syringe
250iu per dose = draw 0.25ml= 25 on the syringe
You can divide all of the above numbers by half if you use 5.5 ml of bacteriostatic water to reconstitute instead of 11 ml. NOTE: Discard all used syringes in a sharps waste container. Most men use 5.5 mls instead of 11 ml to inject smaller volumes under the skin.
What are HCG's effective doses?
A review of the literature reveals a wide range of doses of HCG used and that there is very little agreement among physicians. For male infertility, doses of HCG used alone range from 1250 IU three times weekly to 5000- 3000 IU twice weekly (these studies did not include men on testosterone replacement). A small study showed that men on testosterone replacement therapy who used 500 IU of HCG every other day were able to remain fertile (testosterone replacement can reduce sperm count).
How long does the boost in testosterone last after an injection of HCG? A study looked into that and also tried to determine if high doses would be more effective at sustaining that boost. The profiles of plasma testosterone and HCG in normal adult men were studied after the administration of 6000 IU HCG under two different protocols. In the first protocol, seven subjects received a single intramuscular injection. Plasma testosterone increased sharply (1.6 0.1-fold) within 4 hours. Then testosterone decreased slightly and remained at a plateau level for at least 24 hours. A delayed peak of testosterone (2.4 0.3-fold) was seen between 7296 hours. Thereafter, testosterone declined and reached the initial levels at 144 hours. In the second protocol, six subjects received two intravenous (IV) injections of HCG (5-8 times the dose given by injection to the first group) at 24-hour intervals. The initial increment of plasma testosterone after the first injection was similar to that seen in the first protocol despite the fact that plasma HCG levels were 58 times higher in this case. At 24 hours, testosterone levels were again lower than those observed at 24 hours and a second IV injection of HCG did not induce a significant increase. The delayed peak of plasma testosterone (2.2 0.2-fold of control) was seen about 24 hour later than that in the first protocol. So, this study shows that more is not better when dosing HCG. In fact, high doses may desensitize Leydig cells in the testicles (this is also a highly debated issue). It also showed that testosterone blood levels peak not once but twice after HCG injections. I wish they had studied a lower dose than 6000 IU since very few physicians prescribe this high dose.
HCG may not only boost testosterone but also increase the number of Leydig cells in the testicles. It is well known that Leydig cell clusters in adult testes enlarge considerably under treatment with HCG. However, it has been uncertain in the past whether this expansion involves an increase in the number of Leydig cells or merely an enlargement of the individual cells. A study was performed in which adult male Sprague-Dawley rats were injected subcutaneously daily with 100 IU HCG for up to 5 weeks. The volume of Leydig cell clusters increased by a factor of 4.7 during the 5 weeks of HCG treatment. The number of Leydig cells (initially averaging 18.6 x 106/cm3 testis) increased to 3 times the control value by 5 weeks of treatment (P<0.001), while the average volume of individual Leydig cells (initially ~2200 m3) enlarged only 1.6 times. They concluded that chronic treatment with HCG increases the number of Leydig cells in the testes of adult rats. We do not know if these results can be extrapolated to men but this observation may explain why HCG restores testicular size in men who have used testosterone without it.
Currently, there are no HCG guidelines for men who need to be on testosterone replacement therapy and want to maintain normal testicular size. A study that used 200 mg per week of testosterone enanthate injections with HCG at doses of 125, 250, or 500 IU every other day in healthy younger men showed that doses above 250 IU every other day preserved normal testicular function (no testicular size measurements were taken, however). Whether this does is effective in older men is yet to be proven. Also, there are no long-term studies using HCG for more than 2 years.
Due to its effect on testosterone, HCG use can also increase estradiol and DHT, although I have not seen data that shows if this increase is proportional to the dose used.
So, the best dose of HCG to sustain normal testicular function while keeping estradiol and DHT conversion to a minimum has not been established since every man is different.
Some doctors are recommending using 200-500 IUs twice or three times a week for men who are concerned about testicular size or who want to preserve fertility while on testosterone replacement. Higher doses, such as 1,000 to 5,000 IUs twice a week, have been used but I believe that these higher doses could cause more estrogen and DHT-related side effects, and possibly desensitize the testicles for HCG in the long term. Some doctors check estradiol levels a month after this protocol is started to determine whether the use of the anastrozole (brand name: Arimidex), is needed to counteract any increases in estradiol levels. High estradiol can cause breast enlargement and water retention in men but it is important at the right blood levels to maintain bone, brain health and possibly sexual function.
Dr. Lipshultz in Houston did an interesting study in men using gels or injections to see if every other day injections of HCG at 500 IU preserved their fertility while on TRT. He found that most men did indeed remain fertile with good sperm quality and count. This study is attached to this post.
For men using testosterone gels, the same dose every third day has anecdotally helped to preserve testicular size (the dose of the gel has to be adjusted after a month of HCG to compensate for the increased testosterone caused by HCG).
Baylor HCG Protocol Based on Desired Pregnancy Timeline:
AAS: Anabolic and androgenic steroids
AA: Semen analysis
Some doctors believe that stopping TRT for a few weeks in which only 2000- 3000 IU HCG weekly is used provides a good way to stimulate testicular function without having to use HCG continuously. I have not seen any data to support this approach in the long term. Others believe that cycling HCG on and off while maintaining TRT may prevent any desensitization of testicular Leydig cells to HCG. Again, no data or reports have been published on this approach.
Some men have asked me why we cannot use HCG solely to make our own testicles produce testosterone without the use of TRT along with it. Using HCG as sole testosterone replacement option may not bring the same subjective benefit on sexual function as pure testosterone delivery systems do even when similar serum androgen levels are produced from comparable baseline values. However, supplementing the more traditional transdermal, or injected options, testosterone with the correct doses of HCG stabilizes blood levels, prevents testicular atrophy, helps rebalance expression of other hormones, and brings reports of a greatly increased sense of well-being and libido. But in excess, HCG can cause acne, water retention, moodiness, and gynecomastia (breast enlargement in men).
Many men have complained that their doctors do not know about HCG and how to use it (I do not blame doctors for being confused!). Some spend a lot of time trying to find doctors to feel comfortable prescribing it. One good way to find out what doctor in your area may be currently prescribing it is to call your local compounding pharmacies to ask them what doctors call them for their patients' prescriptions.
Blood Test to Measure HCG Efficacy: 17-Hydroxyprogesterone
Important Note: Unlike testosterone, HCG is not a DEA controlled substance in most states. However, it is a controlled substance in the following states (state regulations may supersede DEA rules): California, Colorado, Connecticut, Illinois, Indiana, Louisiana, Maine, Nevada, New York, North Carolina, Pennsylvania, Rhode Island.
After reading this information, you probably agree with me that using HCG requires a lot of discipline since you have to remember to inject it weekly in addition to your weekly or bi-weekly testosterone injection. But I know of many men who have that type of commitment since they do not want testicular size reduction. And many of us may just be fine with our reduced testicular size as long as testosterone is actually doing its job in improving our sex drive. And some lucky men do not get testicular atrophy at all on testosterone (those with large testicles to start with usually do not seem to complain about shrinkage as much as men starting with smaller testicular size before TRT). So it is a personal decision at the end!
HCG Use in Men: Main Questions and Answers
HCG FACT SHEET: Click here
Click here to read published studies on the use of HCG in men.
For more information about how to prevent and reverse side effects of testosterone, please read: Testosterone Side Effect Management Table
Human Chorionic Gonadotropin (hCG) studies as follows:
1. Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression
2. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.
Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. - PubMed - NCBI
3. Exogenous testosterone: a preventable cause of male infertility
Exogenous testosterone: a preventable cause of male infertility - Crosnoe - Translational Andrology and Urology
4. Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone.
Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone. - PubMed - NCBI
5. Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience.
Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experie... - PubMed - NCBI
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